Methods and compositions for wound healing

Abstract

The present invention relates to methods and compositions for wound healing. In particular, the present invention relates to promoting and enhancing wound healing by utilizing cross-linker covalent modification molecules to attach and deliver wound active agents to a wound. In addition, the present invention provides methods and compositions utilizing oppositely charged polymers to form a polyelectrolyte layer on a wound surface. The invention further relates to incorporating wound active agents into a polyelectrolyte layer for delivery to a wound.

What is claimed is: 
     
         1 . A method of treating a wound in a patient in need thereof comprising applying to the wound of the patient in need thereof a membrane comprising polyelectrolyte multilayer comprising cationic and anionic polymers directly supported on a solid polymeric membrane formed from a polymer that is different from the cationic and anionic polymers ion the polyelectrolyte multilayer, said polyelectrolyte multilayer comprising an antimicrobial compound incorporated therein and having a thickness of from 1 to 1,000 nm and a compliance of from 3 to 500 kPa. 
     
     
         2 . The method of  claim 1 , wherein said antimicrobial agent is distributed within said polyelectrolyte multilayer so that a gradient is formed. 
     
     
         3 . The method of  claim 1 , wherein said antimicrobial agent is a silver antimicrobial compound. 
     
     
         4 . The method of  claim 1 , wherein said antimicrobial agent is selected from the group consisting of loracarbef, cephalexin, cefadroxil, cefixime, ceftibuten, cefprozil, cefpodoxime, cephradine, cefuroxime, cefaclor, neomycin, dicloxacillin, nitrofurantoin, nitrofurantoin macrocrystal, nitrofurantoin/nitrofuran mac, dirithromycin, gemifloxacin, ampicillin, gatifloxacin, ciprofloxacin, enoxacin, amoxicillin, clarithromycin, levofloxacin, moxifloxacin, azithromycin, sparfloxacin, cefdinir, ofloxacin, trovafloxacin, lomefloxacin, erythromycin, norfloxacin, clindamycin, quinupristin, doxycycline, amikacin sulfate, vancomycin, kanamycin, netilmicin, streptomycin, tobramycin sulfate, gentamicin sulfate, tetracycline, framycetin, minocycline, nalidixic acid, demeclocycline, trimethoprim, miconazole, colistimethate, paromomycin, sulfisoxazole, pentamidine, sulfadiazine, clindamycin phosphate, metronidazole, oxacillin sodium, nafcillin sodium, vancomycin hydrochloride, clindamycin, cefotaxime sodium, co-trimoxazole, ticarcillin disodium, piperacillin sodium, ticarcillin disodium/clavulanate potassium, neomycin, daptomycin, cefazolin sodium, cefoxitin sodium, ceftizoxime sodium, penicillin, ceftriaxone sodium, ceftazidime, imipenem, aztreonam, cinoxacin, cefotetan disodium, cefoperazone sodium, cefamandole nafate, gentamicin, tobramycin, lincomycin, alatrofloxacin, linezolid, tetracycline, mupirocin, fosfomycin, pentamidine isethionate, imipenem/cilastatin, troleandomycin, gatifloxacin, chloramphenicol, cycloserine, meropenem, cephalosporins, fluconazole, cefepime, sulfamethoxazole, chloroquine phosphate, and silver sulfadiazine. 
     
     
         5 . The method of  claim 1 , wherein said membrane further comprises an analgesic agent. 
     
     
         6 . The method of  claim 5 , wherein said analgesic agent is selected from the group consisting of acetaminophen, anileridine, acetylsalicylic acid, buprenorphine, butorphanol, fentanyl, fentanyl citrate, codeine, rofecoxib, hydrocodone, hydromorphone, hydromorphone hydrochloride, levorphanol, alfentanil hydrochloride, meperidine, meperidine hydrochloride, methadone, morphine, nalbuphine, opium, levomethadyl, hyaluronate sodium, sufentanil citrate, capsaicin, tramadol, leflunomide, oxycodone, oxymorphone, celecoxib, pentazocine, propoxyphene, benzocaine, lidocaine, dezocine, clonidine, butalbital, phenobarbital, tetracaine, phenazopyridine, sulfamethoxazole/phenazopyridine, and sulfisoxazole/phenazopyridine. 
     
     
         7 . The method of  claim 1 , wherein the cationic polymer is selected from the group consisting of poly(L-lysine), poly(ethylene imine), and poly(allylamine) hydrochloride. 
     
     
         8 . The method of  claim 1 , wherein said anionic polymers are selected from the group consisting of poly(L-glutamic acid), poly(sodium 4-styrenesulfonate), poly(acrylic acid), poly(maleic acid-co-propylene) and poly(vinyl sulfate). 
     
     
         9 . The method of  claim 1 , wherein said wound of said patient is a chronic wound. 
     
     
         10 . The method of  claim 9 , wherein said wound of said patient is an ulcer. 
     
     
         11 . The method of  claim 9 , wherein said ulcer is selected from the group consisting of a neuropathic ulcer, a diabetic ulcer, a venous stasis ulcer and a pressure sore. 
     
     
         12 . The method of  claim 1 , wherein said wound is a burn wound. 
     
     
         13 . The method of  claim 1 , wherein said wound is selected from the group consisting of a cut, an abrasion, and a surgical incision site. 
     
     
         14 . A method of treating a wound in a patient in need thereof comprising applying to the wound of the patient in need thereof a membrane comprising polyelectrolyte multilayer comprising cationic and anionic polymers directly supported on a solid polymeric membrane formed from a polymer that is different from the cationic and anionic polymers ion the polyelectrolyte multilayer, said polyelectrolyte multilayer comprising an antimicrobial compound incorporated therein and having a thickness of from 1 to 1,000 nm and a compliance of from 3 to 500 kPa,
 wherein said wound is an ulcer selected from the group consisting of a neuropathic ulcer, a diabetic ulcer, a venous stasis ulcer and a pressure sore. 
 
     
     
         15 . A method of treating a wound in a patient in need thereof comprising applying to the wound of the patient in need thereof a membrane comprising polyelectrolyte multilayer comprising cationic and anionic polymers directly supported on a solid polymeric membrane formed from a polymer that is different from the cationic and anionic polymers ion the polyelectrolyte multilayer, said polyelectrolyte multilayer comprising an antimicrobial compound incorporated therein and having a thickness of from 1 to 1,000 nm and a compliance of from 3 to 500 kPa,
 wherein said wound is a chronic wound.   
     
     
         16 . A method of treating a wound in a patient in need thereof comprising applying to the wound of the patient in need thereof a membrane comprising polyelectrolyte multilayer comprising cationic and anionic polymers directly supported on a solid polymeric membrane formed from a polymer that is different from the cationic and anionic polymers ion the polyelectrolyte multilayer, said polyelectrolyte multilayer comprising an antimicrobial compound incorporated therein and having a thickness of from 1 to 1,000 nm and a compliance of from 3 to 500 kPa,
 wherein said wound is a burn wound.   
     
     
         17 . A method of treating a wound in a patient in need thereof comprising applying to the wound of the patient in need thereof a membrane comprising polyelectrolyte multilayer comprising cationic and anionic polymers directly supported on a solid polymeric membrane formed from a polymer that is different from the cationic and anionic polymers ion the polyelectrolyte multilayer, said polyelectrolyte multilayer comprising an antimicrobial compound incorporated therein and having a thickness of from 1 to 1,000 nm and a compliance of from 3 to 500 kPa,
 wherein said wound is selected from the group consisting of a cut, an abrasion, and a surgical incision site.